From dysregulated microRNAs to structural alterations in the striatal region of METH-injected rats
From dysregulated microRNAs to structural alterations in the striatal region of METH-injected rats
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DOI：
10.1016/j.jchemneu.2020.101854
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发表时间：
2020-11-01
影响因子：
2.8
通讯作者：
Aliaghaei, Abbas
中科院分区：
文献类型：
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作者：
Chavoshi, Hossein;Boroujeni, Mahdi Eskandarian;Aliaghaei, Abbas
甲基苯丙胺（Methamphetamine，简称冰毒）是一种高成瘾性的精神兴奋剂，可通过神经元变性引发脑萎缩。纹状体是大脑的主要部位，被认为是药物性损伤的关键靶点。mirna作为转录后水平的小调控分子，在生物通路中发挥着重要作用。在本研究中，我们首先对服用冰毒的大鼠进行了行为评估。然后，我们检测纹状体体积和树突长度，并免疫组织化学检测酪氨酸羟化酶（TH）、caspase-3和胶质纤维酸性蛋白（GFAP）的水平。此外，我们使用高通量小RNA-seq技术研究了miRNA表达谱。根据我们的数据，甲基安非他命引起运动协调性下降，纹状体体积和树突长度减少以及星形胶质细胞过度激活。此外,冰毒治疗抑制TH水平虽然诱导上调caspase-3的纹状体区域。此外，通过miR-seq分析，我们在纹状体中发现167个mirna在甲基苯甲胺处理后失调，其中rno-let-7b-5p、rno-miR-485-5p、rno-miR-326-3p、rno-miR-34a-5p、rno-miR-3068-5p表现出高mirna -靶基因相互作用。通路分析显示，mirna及其靶基因可能参与细胞凋亡、生长、分化以及突触可塑性相关通路。总之，我们可以得出结论，甲基苯丙胺明显引起背纹状体的新变性。
Methamphetamine (METH) is a high addictive psychostimulant drug which triggers brain atrophy via neuronal degeneration. Striatum is the main part of the brain that is regarded as a key target for drug-induced damages. MiRNAs as small regulatory molecules at the post-transcriptional level play a major role in biological pathways. In this study, initially we performed behavioral assessment in METH-treated rats. Then, we examined striatal volume and dendritic length, and also the levels of tyrosine hydroxylase (TH), caspase-3 and glial fibrillary acidic protein (GFAP) were immunohistochemically assessed. Moreover, we investigated miRNA expression profiling using high-throughput small RNA-seq technology. Based on our data, METH provoked declined motor coordination, decreases in striatal volume and dendritic length along with over-activation of astrogliosis. In addition, METH treatment down-regulated TH level while it induced up-regulation of caspase-3 in the striatal region. Furthermore, according to miR-seq analysis, we found 167 deregulated miRNAs in the striatum upon METH treatment, that among them rno-let-7b-5p, rno-miR-485-5p, rno-miR-326-3p, rno-miR-34a-5p, rno-miR-3068-5p showed high miRNA-target gene interaction. Pathway analysis revealed that miRNAs and their target genes may be involved in cell apoptosis, growth, differentiation as well as synaptic plasticity associated pathways. Altogether, we can conclude that METH noticeably elicited neum-degeneration in the dorsal striatum.